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[“乙肝病毒‘a’决定簇热点”突变对乙肝疫苗疗效的作用]

[Role of mutations on the "hepatitis B virus 'a' determinant hotpoint" to the efficacy of hepatitis B vaccine].

作者信息

Zhang Rui, Li Rong-cheng, Zhu Feng-cai, Li Yan-ping, Liu She-lan, Zhang Xian-chen, Wang Sheng-qi, Liang Zheng-lun, Li He-min, Zhuang Hui

机构信息

National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2007 Apr;28(4):334-7.

Abstract

OBJECTIVE

To study how hepatitis B virus(HBV) 'a' determinant hotpoint mutations were influecing the hepatitis B vaccine efficacy.

METHODS

Primers were designed in HBV conservative region, and the degenerate probes for detecting 16 'a' determinant hotpoint mutations were developed for gene chips. Sensitivity and specificity of the gene chips were evaluated by clone sequencing. Sera of 47 pairs of mothers and infants with immune failure and 323 mothers of children with immune protection of HB vaccine were detected by the gene chips.

RESULTS

Result from clone sequencing demonstrated that the gene chips were specific for the detection of 'a' determinant hotpoint mutations. The wild type of HBV was still dominant, with the prevalence of 78.66%, and the mutation frequencies of 126A, 145R, 126S-1, 126S-2, 129H, 144A, and 129R were 11.27%, 5.76%, 5.28%, 4.56%, 1.20%, 0.72% and 0.24%, respectively. The prevalence of 126A mutation was significantly higher than that of other mutations(P < 0.01). No significant differences were found in mother-infant transmission rates of 126A, 126S-1, 126S-2 and 145R variants.

CONCLUSION

The currently available hepatitis B vaccine could block mother-infant transmission of 126A, 126S and 145R variants. It appears that there is no need to develop a new hepatitis B vaccine against 126 and 145 variants at present, but the consistent epidemiological surveillance on HBV mutants should be carried out.

摘要

目的

研究乙型肝炎病毒(HBV)“a”决定簇热点突变如何影响乙型肝炎疫苗的效力。

方法

在HBV保守区设计引物,并开发用于基因芯片检测16个“a”决定簇热点突变的简并探针。通过克隆测序评估基因芯片的灵敏度和特异性。用该基因芯片检测47对免疫失败母婴和323名乙肝疫苗免疫成功儿童母亲的血清。

结果

克隆测序结果表明,该基因芯片对“a”决定簇热点突变的检测具有特异性。HBV野生型仍占主导,流行率为78.66%,126A、145R、126S-1、126S-2、129H、144A和129R的突变频率分别为11.27%、5.76%、5.28% 、4.56%、1.20%、0.72%和0.24%。126A突变的流行率显著高于其他突变(P<0.01)。126A、126S-1、126S-2和145R变异体的母婴传播率无显著差异。

结论

目前可用的乙型肝炎疫苗可阻断126A、126S和145R变异体的母婴传播。目前似乎没有必要开发针对126和145变异体的新型乙型肝炎疫苗,但应持续对HBV突变体进行流行病学监测。

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